UniProtKB/Swiss-Prot O75648: Variant p.Ala10Ser

Mitochondrial tRNA-specific 2-thiouridylase 1
Gene: TRMU
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Variant information Variant position:

10 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Alanine (A) to Serine (S) at position 10 (A10S, p.Ala10Ser). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from small size and hydrophobic (A) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

1 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

Acts as a disease modifier in patients with aminoglycoside-induced deafness and a mutation in mitochondrial 12S rRNA; affects tRNA processing by decreasing thiolation and increasing aminoacylation of tRNAs; the mutant has lower thermal stability than wild-type; does not affect import in the mitochondria. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs11090865 [ dbSNP | Ensembl ]

Sequence information Variant position:

10 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

421 The length of the canonical sequence.
Location on the sequence:

MQALRHVVC A LSGGVDSAVAALLLRRRGYQ The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         MQALRHVVCALSGGVDSAVAALLLRRRGYQ

Mouse                         MSALRHVVCALSGGVDSAVAALLLRRRGYQ

Rat                           MSALRHVVCALSGGVDSAVAALLLRRRGYQ

Chicken                       LAAGRRVACAVSGGVDSAVAALLLRRRGYQ

Zebrafish                     MGVLRHVVCAMSGGVDSSVSALLLKRMGYH

Caenorhabditis elegans        ---MPRVVIGMSGGVDSAVSAFLLKKRGFD

Drosophila                    --MIRNVVVGVSGGVDSAVSAHLLAEQGFK

Slime mold                    LPKKPKVCIGMSGGVDSTITAKLLKLQGFD

Baker's yeast                 PAKFDNVIVAMSSGVDSSVAAALFAGEFPN

Fission yeast                 PKSQDKVFVAMSGGVDSSFSAYLLKSQGYN

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 421	Mitochondrial tRNA-specific 2-thiouridylase 1
Binding site	10 – 17
Alternative sequence	1 – 154	Missing. In isoform 3 and isoform 4.
Mutagenesis	16 – 16	D -> A. Loss of activity.

Literature citations
Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitochondrial 12S ribosomal RNA mutations.
Guan M.-X.; Yan Q.; Li X.; Bykhovskaya Y.; Gallo-Teran J.; Hajek P.; Umeda N.; Zhao H.; Garrido G.; Mengesha E.; Suzuki T.; del Castillo I.; Peters J.L.; Li R.; Qian Y.; Wang X.; Ballana E.; Shohat M.; Lu J.; Estivill X.; Watanabe K.; Fischel-Ghodsian N.;
Am. J. Hum. Genet. 79:291-302(2006)
Cited for: INVOLVEMENT IN DFNI; VARIANT SER-10; CHARACTERIZATION OF VARIANT SER-10; FUNCTION; SUBCELLULAR LOCATION; Acute infantile liver failure due to mutations in the TRMU gene.
Zeharia A.; Shaag A.; Pappo O.; Mager-Heckel A.-M.; Saada A.; Beinat M.; Karicheva O.; Mandel H.; Ofek N.; Segel R.; Marom D.; Roetig A.; Tarassov I.; Elpeleg O.;
Am. J. Hum. Genet. 85:401-407(2009)
Cited for: VARIANTS LFIT HIS-77 AND ASP-272; VARIANTS SER-10; SER-14 AND MET-279; Biochemical evidence for a nuclear modifier allele (A10S) in TRMU (Methylaminomethyl-2-thiouridylate-methyltransferase) related to mitochondrial tRNA modification in the phenotypic manifestation of deafness-associated 12S rRNA mutation.
Meng F.; Cang X.; Peng Y.; Li R.; Zhang Z.; Li F.; Fan Q.; Guan A.S.; Fischel-Ghosian N.; Zhao X.; Guan M.X.;
J. Biol. Chem. 292:2881-2892(2017)
Cited for: CHARACTERIZATION OF VARIANT SER-10;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.